Confirmatory Tests for the Diagnosis of Primary Aldosteronism

A Systematic Review and Meta-Analysis

Sicen Wu; Jun Yang; Jinbo Hu; Ying Song; Wenwen He; Shumin Yang; Rong Luo; Qifu Li


Clin Endocrinol. 2019;90(5):641-648. 

In This Article

Abstract and Introduction


Objective: Saline infusion test (SIT), captopril challenge test (CCT), fludrocortisone suppression test (FST) and oral sodium loading test (SLT) are recommended by the Endocrine Society's Clinical Practice Guidelines to diagnose primary aldosteronism, but which one is the best remains controversial. We aimed to summarize the available comparative data and evaluate the diagnostic accuracy of these four tests.

Design: We searched PubMed, Embase and the Cochrane Library for relevant studies published between January 1980 and January 2018.

Patients: Eligible studies reported on the accuracy of one or more of the four confirmatory tests in patients suspected of PA.

Measurements: Two reviewers independently conducted the data extraction of all selected studies, which consisted of study characteristics and data to estimate the summary receiver operating characteristic (SROC) curve and the corresponding summary area under the curve (SAUC), pooled sensitivity and specificity, diagnostic odds ratios (DOR) with 95% confidence interval (CI).

Results: We identified 26 articles including 3686 patients. Fifteen articles evaluated the diagnostic accuracy of CCT, 10 of SIT, 1 of FST and none of SLT. For CCT, the SAUC was 0.9207, and the pooled sensitivity and specificity were 0.87 (95% CI: 0.84-0.89) and 0.84 (95% CI: 0.81-0.86), respectively. For SIT, the SAUC was 0.9232, and the pooled sensitivity and specificity were 0.85 (95% CI: 0.82-0.87) and 0.87 (95% CI: 0.85-0.89), respectively. For FST, the pooled sensitivity and specificity were 0.87 (95% CI: 0.66-0.97) and 0.95 (95% CI: 0.82-0.99), respectively. Overall, we found no significant differences in the diagnostic accuracy of CCT and SIT.

Conclusions: CCT and SIT exhibit high and comparable accuracy for diagnosing PA. CCT may be a more feasible alternative as it is safe and much easier to perform.


Primary aldosteronism (PA) is recognized as a common cause of secondary hypertension, possibly accounting for around 6% of the general hypertensive population and 11% of the tertiary care referral centres.[1] The accurate diagnosis of PA is of utmost importance as patients with PA experience worse cardiovascular and renal outcomes than those with blood pressure-matched essential hypertension (EH).[2–5]

The diagnostic pathway of PA consists of three phases: screening, confirmation and subtype classification. The Endocrine Society's Clinical Practice Guidelines recommended four confirmatory tests, including saline infusion test (SIT), captopril challenge test (CCT), fludrocortisone suppression test (FST) and oral sodium loading test (SLT).[6] Each test has its own advantages and disadvantages. For SIT, although it is widely used and reliable, it is contraindicated in patients with renal insufficiency or congestive heart failure.[7] CCT is safe, less expensive and easily performed in outpatient clinics, but the dose of captopril, the time points for blood sampling and the diagnostic criteria remain controversial.[8] FST has been considered the most reliable test, but it is cumbersome and expensive to conduct.[9–11] SLT is the cheapest, but urinary aldosterone cannot be measured accurately and patient compliance with 24 hour urine collection is a key limitation.[12]

To date, studies comparing the diagnostic accuracy of one confirmatory test to another are few, and which one is the best remains controversial. For example, when comparing CCT with SIT, Meng et al[13] found that the area under the curve (AUC) was 0.972 for plasma aldosterone concentration (PAC) post-SIT and 0.933 for PAC post-CCT, the positive predictive values were 97.2% and 96.1% for SIT and CCT, whereas the negative predictive values were 80.7% and 75.0% respectively, which indicated that the SIT may have a slight advantage over the CCT. However, our previous study[14] found that the AUC of PAC post-SIT was 0.96, with a 85% sensitivity and 92% specificity, and the AUC of PAC post-CCT was 0.96, with a 90% sensitivity and 90% specificity, but no significant differences were found between SIT and CCT. To reduce the uncertainty around confirmatory tests, we set out to perform a systematic review and meta-analysis of existing data and compare the diagnostic accuracy of these four confirmatory tests.